Search

BACKGROUND AND AIMS: Digital single-operator cholangioscopy (d-SOC) with cholangioscopic biopsy sampling has shown promise in the evaluation of indeterminate biliary strictures. Some studies have suggested higher sensitivity for visual impression compared with biopsy sampling, although assessors were not blinded to previous investigations. We aimed to investigate the diagnostic accuracy and interobserver agreement (IOA) of d-SOC in the visual appraisal of biliary strictures when blinded to additional information. METHODS: A multicenter, international cohort study was performed. Cholangioscopic videos in patients with a known final diagnosis were systematically scored. Pseudonymized videos were reviewed by 19 experts in 2 steps: blinded for patient history and investigations and unblinded. RESULTS: Forty-four high-quality videos were reviewed of 19 benign and 25 malignant strictures. The sensitivity and specificity for the diagnosis of malignancy was 74.2% and 46.9% (blinded) and 72.7% and 62.5% (unblinded). Cholangioscopic certainty of a malignant diagnosis led to overdiagnosis (sensitivity, 90.6%; specificity, 33%), especially if no additional information was provided. The IOA for the presence of malignancy was fair for both assessments (Fleiss' κ = .245 [blinded] and κ = .321 [unblended]). For individual visual features, the IOA ranged from slight to moderate for both assessments (κ = .059-.400 vs κ = .031-.452). CONCLUSIONS: This study showed low sensitivity and specificity for blinded and unblinded d-SOC video appraisal of indeterminate biliary strictures, with considerable interobserver variation. Although reaching a consensus on the optical features of biliary strictures remains important, optimizing visually directed biopsy sampling may be the most important role of cholangioscopy in biliary stricture assessment. ispartof: GASTROINTESTINAL ENDOSCOPY vol:94 issue:6 pages:1059-1068 ispartof: location:United States status: published

ObjectiveTo explore impacts of the COVID-19 pandemic on patterns of sickness absence among staff employed by the National Health Service (NHS) in England.MethodsWe analysed prospectively collected, pseudonymised data on 959,356 employees who were continuously employed by NHS trusts during 1 January 2019 to 31 July 2020, comparing the frequency of new sickness absence in 2020 with that at corresponding times in 2019.ResultsAfter exclusion of episodes directly related to COVID-19, the overall incidence of sickness absence during the initial 10 weeks of the pandemic (March-May 2020) was more than 20% lower than in corresponding weeks of 2019, but trends for specific categories of illness varied. Marked increases were observed for asthma (122%), infectious diseases (283%) and mental illness (42.3%), while reductions were apparent for gastrointestinal problems (48.4%), genitourinary/gynaecological disorders (33.8%), eye problems (42.7%), injury and fracture (27.7%), back problems (19.6%), other musculoskeletal disorders (29.3%), disorders of ear, nose and throat (32.7%), cough/flu (24.5%) and cancer (24.1%). A doubling of new absences for pregnancy-related disorders during 18 May to 19 July of 2020 was limited to women with earlier COVID-19 sickness absence.ConclusionsVarious factors will have contributed to the large and divergent changes that were observed. The findings add to concerns regarding delays in diagnosis and treatment of cancers, and support a need to plan for a large backlog of treatment for many other diseases. Further research should explore the rise in absence for pregnancy-related disorders among women with earlier COVID-19 sickness absence.1. What is already known about this subject?Historically, rates of sickness absence among the NHS workforce in England have been relatively high but stable. Reports of a marked increase during the first wave of the COVID-19 pandemic have not distinguished between different categories of underlying illness.2. What are the new findings?During the first wave of COVID-19, incidence of sickness-absence changed markedly when compared to the previous year, with major increases for some categories of illness, and large declines for many others, including cancer.3. How might this impact on policy or clinical practice in the foreseeable future?The findings support a need to plan for effects from delayed diagnosis and treatment of cancer, and to manage a large backlog of treatment for many other diseases.

The aim of the study was to analyse health-related quality of life (HRQoL) and its determinants in individuals with an increased risk of developing type 2 diabetes mellitus (T2D). We used pseudonymized baseline data collected between 2018 and 2020 as part of the Dimini project in Hesse and Schleswig–Holstein. HRQoL was measured by the mental and the physical component score of the validated instrument Short Form 12 and descriptively analysed followed by multiple linear regression analysis. The Dimini population (n = 662) showed an average physical component score of 42.12 (SD 10.56) and a mental component score of 47.12 (SD 11.13). While men demonstrated both significantly higher physical and mental component scores than women, differences based on migration background were not observed. Younger age was associated with a higher level of the physical component score, whereas mental component scores linearly increased with age. Regarding indicators of T2D-risk, a significant influence of HbA1c on HRQoL was not confirmed. However, physical component scores are negatively related to Findrisk scores and BMI. Finally, study participants living alone and those with a handicap reported lower levels of HRQoL. Compared with a representative sample of the general German population (DEGS1), Dimini participants were characterized by a lower average HRQoL. The analysis showed a higher vulnerability to an impaired HRQoL within certain subgroups of the population and among participants with relatively higher levels of T2D-risk. As a result, tailored healthcare interventions are required to reach these target groups. Trial Registration Number: ClinicalTrials.gov ID NCT03482674.

Összefoglaló. Bevezetés: Mivel hazánkban a sclerosis multiplex gyakoriságáról, valamint életkori és nemi jellegzetességeiről az elmúlt évtizedekben – egészen 2020-ig – csak regionális jellegű felmérések készültek egy-egy centrum betegforgalma alapján, az újonnan diagnosztizált és már ismert betegek országos koreloszlásáról és annak időbeli változásairól nincsenek ismereteink. Célkitűzés: Jelen munkánkban több mint 14 000 beteg adatainak elemzésével a prevalens és incidens betegek koreloszlásának változását vizsgáljuk 2004–2016 során, és eredményeinket összevetjük az elmúlt évtizedekben közölt hazai adatokkal. Módszer: Munkacsoportunk az egészségbiztosítási pénztár anonimizált NEUROHUN adatbázisát elemezte, amely tartalmazza a 2004 és 2016 között az összes hazai, államilag finanszírozott, a fekvő- és járóbeteg-szakellátásból neurológiai diagnózissal jelentett esetet. A sclerosis multiplex BNO-kódjának előfordulása alapján korábban létrehoztuk a betegség adminisztratív definícióját, és megbecsültük a sclerosis multiplex országos prevalenciáját és incidenciáját. Eredmények: A prevalens betegek átlagéletkora 2015-ben 47,9 év, ugyanebben az évben az incidens betegek átlagéletkora 37,4 év volt. Vizsgálatunk szerint a prevalens betegek átlagéletkora szignifikánsan – évente egyötöd–egyharmad évvel (pKövetkeztetés: Eredményeink szerint az újonnan diagnosztizált sclerosis multiplexes páciensek átlagosan egyre fiatalabbak, és a prevalens betegek között is egyre fiatalabb korosztályok a legnépesebbek, de a javuló túlélés és a hosszabb élettartam miatt a prevalens betegek átlagéletkora összességében valószínűleg fokozatosan emelkedik. Orv Hetil. 2021; 162(19): 746–753. Summary. Introduction: The nationwide age and gender distribution of newly diagnosed and prevalent multiple sclerosis patients has been unknown in Hungary, as until 2020 only regional studies had been reported about the frequency and age characteristics of subjects with multiple sclerosis, based on single-center patient registries. Objective: In the present study with the analysis of over 14 000 patients, we describe the changes in age distribution of prevalent and incident subjects between 2004 and 2016 and compare our results with the data published on the subject during the last decades in Hungary. Method: We have analyzed the pseudonymized NEUROHUN database provided by the single-payer National Health Insurance Fund, that contains each claim submitted by public hospitals and outpatient services for neurologic diseases between 2004 and 2016. Using the ICD10-code of multiple sclerosis, we have previously established the administrative definition of the illness and estimated its prevalence and incidence in the country. Results: The mean age of prevalent patients was 47.9 years in 2015, whereas in the same year the mean age of incident cases was 37.4 years. The average age of prevalent patients shows a significant rise – with an annual increase of one fifth–one third year (pConclusion: Our results suggest that though new patients are younger year-by-year and the most populous age groups are also younger, altogether the average age of prevalent subjects continuously increases, probably due to the longer survival and lifespan of patients with multiple sclerosis. Orv Hetil. 2021; 162(19): 746–753.

Background: The aim of this study was to examine the correlation between the risk of increasing kyphosis as well as collapse of the osteoporotic vertebral body fractures and the intensity of the bone edema in magnetic resonance imaging (MRI) scans. Inclusion criteria included the following: age >18 years and osteoporotic vertebral body fracture grade I–IV according to OF classification. Exclusion criteria included the following: other pathological fractures due to primary tumors or metastasis, OF grade V fractures, and AO type B or C fractures. Methods: This was a retrospective study from pseudonymized data of a tertiary spine center. No additional imaging were performed. Measurements of bisegmental kyphosis angle of the fracture for involvement of both endplates and monosegmental angle for involvement of 1 endplate, as well as vertebral body height loss in initial radiographs and at follow-ups after 3 and 6 months have been performed. Also, the initial signal intensity of the vertebral body edema was measured using integrated tool of the DICOM viewer (Impax V6.5 Agfa, Brentford, UK) in addition to the signal intensity of the cerebrospinal fluid (CSF) as reference for T1, T2, and separate target illumination radar (STIR) sequences of the MRI scans. A quotient from the signal intensity of the vertebral body edema and the reference (CSF) has been generated. Patients have been divided to 4 groups according to the ratio ( 3) and compared in regards to the results of the degree of kyphosis and vertebral collapse at follow-ups and final examination. The statistical analysis was performed using linear regression using statistic software SPSS version 26. Results and Conclusions: Forty-four patients have been included: 9 males and 35 females with an average age of 71.5 years. The analysis showed a significant correlation between the increasing kyphosis at follow-ups and the quotient of the signal intensity for STIR and T2 weighing with P = .002 (SD ±2.664) for STIR and P = .001 (SD ±1.616) for T2 sequences. Furthermore, there was only a correlation between the intensity ratio and kyphosis for STIR weighting at last examination (P = .017; SD ±1.360). There was no correlation between the height loss and the signal intensity. Level of Evidence: Level 2

Objectives Preoperative planning of lung resection extent is decisive for preoperative functional work-up and selection for multimodal treatment. It is mainly based on preoperative chest CT. We aimed at evaluating chest CT adequacy to predict the extent of lung resection and hypothesized a relation with CT interpreters’ level of experience. Materials and Methods A pseudonymized CT library was built from patients who had curative intent lung resection for centrally located NSCLC. CT library was interpreted by 20 thoracic surgery residents or attendings. Interpreters were blinded to intraoperative findings and scored one point when lung resection was adequately planned. Points were summed up in a score from 0 to 20. Interpreters’ experience was evaluated through nine variables: age, position (resident vs. attending), years of experience in evaluating chest CTs, number of anatomic resections and sleeve resections attended as first assistant or performed as surgeon in presence of a teaching assistant or as main surgeon/teaching assistant. Variables characterizing interpreters’ experience were divided into equal sized groups. Independent sample T-test and one-way ANOVA/Tukey post hoc tests were used to compare scores between groups. Results CT library included 20 patients. Lung resections were lobectomy (n = 7, 35 %), sleeve lobectomy (n = 10, 50 %), sleeve bilobectomy (n = 2, 10 %), pneumonectomy (n = 1, 5%). Twenty interpreters scored a median of 10 (4–14). Attending surgeons had significantly higher mean scores (11.2 ± 1.3) compared to residents (7.7 ± 2.3, p = 0.001). All scores were significantly different between groups related to interpreters’ levels of experience, except for interpreters’age. Conclusion Preoperative CT evaluation for predicting intraoperative lung resection for centrally located NSCLC strongly depends on interpreters’ experience.

Introduction The majority of pediatric surgeons and hepatologists recommend the centralization of biliary atresia (BA) treatment within experienced liver units. We aimed to investigate whether voluntary self-restriction and acceptance of the need for this change in practice changed the BA referral policy in Germany during the last decade. Materials and Methods In cooperation with pediatric surgeons, gastroenterologists or hepatologists, and pediatric liver transplant units, the 2-year follow-up data of infants with BA born in Germany between 2010 and 2014 were collected using www.bard-online.com or pseudonymized data transfer. Results were compared with our previous analysis of the outcome data of infants with BA born between 2001 and 2005 in Germany. Result Overall, 173 infants with BA were identified, of whom 160 underwent Kasai portoenterostomy (KPE; 92.5%) and 13 (7.5%) underwent primary liver transplantation at 21 German centers. At 2-year follow-up, overall survival was 87.7% (vs. 81.9% in 2001–2005 [p = 0.19]), survival with native liver post-KPE was 29.2% (vs. 22.8% in 2001–2005 [p = 0.24]), and jaundice-free survival with native liver post-KPE was 24.0% (vs. 20.1% in 2001–2005 [p = 0.5]). Compared with the 2001–2005 analysis, all criteria showed improvement but the differences are statistically not significant. Conclusion Our observation shows that KPE management requires improvement in Germany. Centralization of BA patients to German reference liver units is not yet mandatory. However, European and national efforts with regard to the centralization of rare diseases support our common endeavor in this direction.

Background Gene drive technologies (GDTs) promote the rapid spread of a particular genetic element within a population of non-human organisms. Potential applications of GDTs include the control of insect vectors, invasive species and agricultural pests. Whether, and if so, under what conditions, GDTs should be deployed is hotly debated. Although broad stances in this debate have been described, the convictions that inform the moral views of the experts shaping these technologies and related policies have not been examined in depth in the academic literature. Methods In this qualitative study, we interviewed GDT experts (n = 33) from different disciplines to identify and better understand their moral views regarding these technologies. The pseudonymized transcripts were analyzed thematically. Results The respondents’ moral views were principally influenced by their attitudes towards (1) the uncertainty related to GDTs; (2) the alternatives to which they should be compared; and (3) the role humans should have in nature. Respondents agreed there is epistemic uncertainty related to GDTs, identified similar knowledge gaps, and stressed the importance of realistic expectations in discussions on GDTs. They disagreed about whether uncertainty provides a rationale to refrain from field trials (‘risks of intervention’ stance) or to proceed with phased testing to obtain more knowledge given the harms of the status quo (‘risks of non-intervention’ stance). With regards to alternatives to tackle vector-borne diseases, invasive species and agricultural pests, respondents disagreed about which alternatives should be considered (un)feasible and (in)sufficiently explored: conventional strategies (‘downstream solutions’ stance) or systematic changes to health care, political and agricultural systems (‘upstream solutions’ stance). Finally, respondents held different views on nature and whether the use of GDTs is compatible with humans’ role in nature (‘interference’ stance) or not (‘non-interference stance’). Conclusions This interview study helps to disentangle the debate on GDTs by providing a better understanding of the moral views of GDT experts. The obtained insights provide valuable stepping-stones for a constructive debate about underlying value conflicts and call attention to topics that deserve further (normative) reflection. Further evaluation of these issues can facilitate the debate on and responsible development of GDTs.

Objectives To facilitate clinical and translational research, imaging and non-imaging clinical data from multiple disparate systems must be aggregated for analysis. Study participant records from various sources are linked together and to patient records when possible to address research questions while ensuring patient privacy. This paper presents a novel tool that pseudonymizes participant identifiers (PIDs) using a researcher-driven automated process that takes advantage of application-programming interface (API) and the Perl Open-Source Digital Imaging and Communications in Medicine Archive (POSDA) to further de-identify PIDs. The tool, on-demand cohort and API participant identifier pseudonymization (O-CAPP), employs a pseudonymization method based on the type of incoming research data. Methods For images, pseudonymization of PIDs is done using API calls that receive PIDs present in Digital Imaging and Communications in Medicine (DICOM) headers and returns the pseudonymized identifiers. For non-imaging clinical research data, PIDs provided by study principal investigators (PIs) are pseudonymized using a nightly automated process. The pseudonymized PIDs (P-PIDs) along with other protected health information is further de-identified using POSDA. Results A sample of 250 PIDs pseudonymized by O-CAPP were selected and successfully validated. Of those, 125 PIDs that were pseudonymized by the nightly automated process were validated by multiple clinical trial investigators (CTIs). For the other 125, CTIs validated radiologic image pseudonymization by API request based on the provided PID and P-PID mappings. Conclusions We developed a novel approach of an on-demand pseudonymization process that will aide researchers in obtaining a comprehensive and holistic view of study participant data without compromising patient privacy.

Technology has changed the way we approach medical care: health data is constantly being generated, medical discoveries are progressing more rapidly, and individuals are more connected across the world than ever before. Backpack Health is a global personal health record platform that harnesses the power of technology to connect users to their primary health data sources, the medical community, and researchers. By syncing with existing patient portals, health data can be stored on the Backpack Health platform and easily accessed and controlled by users in one connected interface. Individuals manage and collate their current and past conditions, genetic test results, symptoms, medications, procedures, labs, and other health data. Users are empowered to disseminate their information to clinicians, researchers, foundations, and pharmaceutical and biotechnology companies they connect with through the Backpack Health application. Here, we describe how two rare disease advocacy groups, The Marfan Foundation and Project Alive, utilize Backpack Health to connect with their target populations. Through secure transfer of pseudonymized data, groups can query their members to improve understanding of clinical features and to facilitate meaningful research. Responses to the groups' surveys show strong member engagement with high completion rates and increases in new Backpack Health users when surveys are deployed. Data from these surveys have been published and used to better inform clinical outcomes for treatment trials. By connecting users directly to the foundations, clinicians, researchers, and industry partners working on their condition, Backpack Health is instrumental in fast-tracking medical discoveries and treatment for rare diseases.

Background Learning from routine healthcare data is important for the improvement of the quality of care. Providing feedback on clinicians’ performance in comparison to their peers has been shown to be more efficient for quality improvements. However, the current methods for providing feedback do not fully address the privacy concerns of stakeholders. Methods The paper proposes a distributed architecture for providing feedback to clinicians on their clinical performances while protecting their privacy. The indicators for the clinical performance of a clinician are computed within a healthcare institution based on pseudonymized data extracted from the electronic health record (EHR) system. Group-level indicators of clinicians across healthcare institutions are computed using privacy-preserving distributed data-mining techniques. A clinician receives feedback reports that compare his or her personal indicators with the aggregated indicators of the individual’s peers. Indicators aggregated across different geographical levels are the basis for monitoring changes in the quality of care. The architecture feasibility was practically evaluated in three general practitioner (GP) offices in Norway that consist of about 20,245 patients. The architecture was applied for providing feedback reports to 21 GPs on their antibiotic prescriptions for selected respiratory tract infections (RTIs). Each GP received one feedback report that covered antibiotic prescriptions between 2015 and 2018, stratified yearly. We assessed the privacy protection and computation time of the architecture. Results Our evaluation indicates that the proposed architecture is feasible for practical use and protects the privacy of the patients, clinicians, and healthcare institutions. The architecture also maintains the physical access control of healthcare institutions over the patient data. We sent a single feedback report to each of the 21 GPs. A total of 14,396 cases were diagnosed with the selected RTIs during the study period across the institutions. Of these cases, 2924 (20.3%) were treated with antibiotics, where 40.8% (1194) of the antibiotic prescriptions were narrow-spectrum antibiotics. Conclusions It is feasible to provide feedback to clinicians on their clinical performance in comparison to peers across healthcare institutions while protecting privacy. The architecture also enables monitoring changes in the quality of care following interventions.

Introduction: Approximately 1 out of 4 stroke patients suffers ischemic stroke secondary to atrial fibrillation (AF). Although indicated, withholding of anticoagulants for secondary prevention is a widespread phenomenon. Objective: We examined the longitudinal change of recommendation and prescription of secondary preventive anticoagulation in AF patients in an acute stroke center setting focusing on the impact of the introduction of direct oral anticoagulants (DOACs) and the change of national stroke prevention guidelines. Methods: Consecutive patients admitted with an acute cerebrovascular ischemic event underwent regular diagnostic work-up. Pseudonymized clinical data were entered into the institution’s stroke registry. In those patients with AF, discharge letters were collected and evaluated for temporal trends and affecting factors of recommended and prescribed antithrombotic secondary medication at the time of discharge from hospital. Results: Of 7,175 patients admitted between January 2009 and December 2018, 1,812 (25.3%) suffered stroke caused by AF. Frequency of patients with recommended anticoagulation increased within the observation period from 66.7 to 95.8% (per year; adjusted odds ratio [OR], 1.309; confidence interval [CI], 1.153–1.486). Independently from this time trend, DOAC approval (adjusted OR, 4.026; CI 1.962–8.265) and guideline change (adjusted OR, 2.184; CI, 1.006–4.743) were associated with an increasing frequency of recommendation for anticoagulation. The rate of patients already receiving recommended anticoagulation for secondary prevention at discharge increased from 42.1 to 62.5%. Introduction of DOACs was not associated with this trend, and guideline change was even associated with decreasing frequency of anticoagulated patients at hospital discharge (adjusted OR, 0.641; CI, 0.414–0.991). Fear of early intracerebral bleeding was the most common reason for withholding anticoagulation (37%) at hospital discharge and stayed stable during the observation period. Conclusions: Changing national guidelines with discard of contraindications for anticoagulation and the introduction of DOACs led to a broader recommendation of oral anticoagulation. However, both, new guidelines and DOACs, were not found to be associated with an increasing percentage of patients discharged from our hospital already on recommended anticoagulant prevention. This might be explained by the decreasing length of hospital stay during the study period and a missing evidence of early bleeding risk of DOACs in patients with acute brain infarction. Evidence-based data to close this therapeutic gap are needed.

The California Consumer Privacy Act (CCPA) is perhaps the most influential state-level data privacy law in the United States. It is the first of its kind to provide significant privacy rights to consumers and is likely to be a model for other state privacy laws. It also gives consumers a great deal of control over their personal information (PI).

Background The Coronavirus disease 2019 (COVID-19) pandemic has underlined the urgent need for reliable, multicenter, and full-admission intensive care data to advance our understanding of the course of the disease and investigate potential treatment strategies. In this study, we present the Dutch Data Warehouse (DDW), the first multicenter electronic health record (EHR) database with full-admission data from critically ill COVID-19 patients. Methods A nation-wide data sharing collaboration was launched at the beginning of the pandemic in March 2020. All hospitals in the Netherlands were asked to participate and share pseudonymized EHR data from adult critically ill COVID-19 patients. Data included patient demographics, clinical observations, administered medication, laboratory determinations, and data from vital sign monitors and life support devices. Data sharing agreements were signed with participating hospitals before any data transfers took place. Data were extracted from the local EHRs with prespecified queries and combined into a staging dataset through an extract–transform–load (ETL) pipeline. In the consecutive processing pipeline, data were mapped to a common concept vocabulary and enriched with derived concepts. Data validation was a continuous process throughout the project. All participating hospitals have access to the DDW. Within legal and ethical boundaries, data are available to clinicians and researchers. Results Out of the 81 intensive care units in the Netherlands, 66 participated in the collaboration, 47 have signed the data sharing agreement, and 35 have shared their data. Data from 25 hospitals have passed through the ETL and processing pipeline. Currently, 3464 patients are included in the DDW, both from wave 1 and wave 2 in the Netherlands. More than 200 million clinical data points are available. Overall ICU mortality was 24.4%. Respiratory and hemodynamic parameters were most frequently measured throughout a patient's stay. For each patient, all administered medication and their daily fluid balance were available. Missing data are reported for each descriptive. Conclusions In this study, we show that EHR data from critically ill COVID-19 patients may be lawfully collected and can be combined into a data warehouse. These initiatives are indispensable to advance medical data science in the field of intensive care medicine.

In Germany, the incidence of cervical cancer, a disease caused by human papillomaviruses (HPV), is higher than in neighboring European countries. HPV vaccination has been recommended for girls since 2007. However, it continues to be significantly less well received than other childhood vaccines, so its potential for cancer prevention is not fully realized.To find new starting points for improving vaccination rates, we analyzed pseudonymized routine billing data from statutory health insurers in the PRÄZIS study in the federal state Saarland serving as a model region. We show that lowering the HPV vaccination age to 9 years led to more completed HPV vaccinations already in 2015. Since then, HPV vaccination rates and the proportion of 9-to 11-year-old girls among HPV-vaccinated females have steadily increased. However, HPV vaccination rates among 15-year-old girls in Saarland remained well below 50% in 2019. Pediatricians vaccinated the most girls overall, with a particularly high proportion at the recommended vaccination age of 9-14 years, while gynecologists provided more HPV catch-up vaccinations among 15-17-year-old girls, and general practitioners compensated for HPV vaccination in Saarland communities with fewer pediatricians or gynecologists. We also provide evidence for a significant association between attendance at the U11 or J1 medical check-ups and HPV vaccination. In particular, participation in HPV vaccination is high on the day of U11. However, obstacles are that U11 is currently not funded by all statutory health insurers and there is a lack of invitation procedures for both U11 and J1, resulting in significantly lower participation rates than for the earlier U8 or U9 screenings, which are conducted exclusively with invitations and reminders.Based on our data, we propose to restructure U11 and J1 screening in Germany, with mandatory funding for U11 and organized invitations for HPV vaccination at U11 or J1 for both boys and girls.

The Covid-19 pandemic has sparked online discussion in unprecedented volumes, as citizens use social media to share their opinions and concerns regarding the prevention measures, for instance. Much of such activity takes place under real names on popular platforms such as Facebook and Twitter. However, parallel to these platforms more anonymous spaces remain and flourish, including completely anonymous services such as Secret.ly and Ask.fm, or pseudonymized services such as Reddit. This study focuses on Covid-19 related discussion on mobile social media platform Jodel, an anonymous-by-design social media application that allows messaging users who are geographically close. In this paper, we explore discussions about the Covid-19 pandemic on Jodel in Helsinki, Finland, through the theoretical notion of affective discipline. Our data is collected during a virtual, mobile ethnography that followed the discussions on the #corona channel in Jodel in Helsinki during 2020-21. We argue that the anonymity of Jodel provided its users a space to discuss the restrictive measures in a more relaxed manner than real-name-based social media. This also endows the conversations with deeper and different affective attunement than what public discussion would. While the discussions contain moral judgments, they were also rife with humor, irony and distanced spectatorship of the ongoing pandemic, resonating with the carnivalistic discussion cultures of other anonymous and pseudonymous platforms. We argue that anonymous and ephemeral platforms like Jodel, where identities and histories are nonexistent, bring out the affective dynamics of online discussions, and the related forces that assemble and disassemble communities.

Background: Surveillance programs in low- and middle-income countries (LMICs) have difficulty in obtaining accurate information about congenital anomalies. Methods: As part of the ZikaPLAN project, an International Committee developed an app for the description and coding of congenital anomalies that are externally visible at birth, for use in low resource settings. The “basic” version of the app was designed for a basic clinical setting and to overcome language and terminology barriers by providing diagrams and photos, sourced mainly from international Birth Defects Atlases. The “surveillance” version additionally allows recording of limited pseudonymized data relevant to diagnosis, which can be uploaded to a secure server, and downloaded by the surveillance program data center. Results: The app contains 98 (88 major and 10 minor) externally visible anomalies and 12 syndromes (including congenital Zika syndrome), with definitions and International Classification of Disease v10 -based code. It also contains newborn examination videos and links to further resources. The user taps a region of the body, then selects among a range of images to choose the congenital anomaly that best resembles what they observe, with guidance regarding similar congenital anomalies. The “basic” version of the app has been reviewed by experts and made available on the Apple and Google Play stores. Since its launch in November 2019, it has been downloaded in 39 countries. The “surveillance” version is currently being field-tested. Conclusion: The global birth defects app is a mHealth tool that can help in developing congenital anomaly surveillance in low resource settings to support prevention and care.

Background Atrial fibrillation is a cardiac arrhythmia commonly encountered in a primary care setting. Current screening is limited to pulse palpation and ECG confirmation when an irregular pulse is found. Paroxysmal atrial fibrillation will, however, still be difficult to pick up. With the advent of smartphones, screening could be more cost-efficient by making use of simple applications, lowering the need for intensive screening to discover (paroxysmal) atrial fibrillation. Methods/design This cluster randomized trial will examine the effect of using a smartphone-based application such as FibriCheck® on the detection rate of atrial fibrillation in a Flemish general practice population. This study will be conducted in 22 primary care practices across the Flanders region of Belgium and will last 12 months. Patients above 65 years of age will be divided in control and intervention groups on the practice level. The control group will be subjected to standard opportunistic screening only, while the intervention group will be prescribed the FibriCheck® app on top of this opportunistic screening. The difference in detection rate between control and intervention groups will be calculated at the end of the study. We will use the online platform INTEGO for pseudonymized data collection and analysis, and risk calculation. Discussion Smartphone applications might offer a way to cost-effectively screen for (paroxysmal) atrial fibrillation in a primary care setting. This could open the door for the update of future screening guidelines. Trial registration ClinicalTrials.gov NCT04545723. Registered on September 10, 2020.

Summary Background The German programme for skin cancer screening was established in 2008 with the aim of reducing skin cancer mortality. However, the effectiveness and risk–benefit ratio of the programme remain unclear. Objectives To compare the mortality rates of patients with melanoma who participate in a screening programme to those who do not. Methods A retrospective cohort study, based on pseudonymized health insurance data of 1 431 327 individuals from Saxony, Germany, was conducted for the period 2010–2016. Patients with prevalent and incident melanoma were defined based on diagnosis, medical procedures and prescriptions. Patients who underwent screening and had a first diagnosis of melanoma within 2 years of screening were assigned to the intervention group. Relative survival and Cox regression were used to assess potential differences in mortality. Results We identified 4552 individuals with prevalent and 2475 individuals with incident melanoma. The percentage of screening participants (n = 1801) who had locoregional (4·2% vs. 13·5%) and/or distant metastases (4·3% vs. 8·0%), or who were treated with systemic anticancer therapies (11·6% vs. 21·8%) was lower vs. nonparticipants (n = 674). Screening participants had significantly better survival rates. The unadjusted Cox model gave a hazard ratio (HR) of 0·37 [95% confidence interval (CI) 0·30–0·46]. After adjusting for named confounders, the effect remained (HR 0·62, 95% CI 0·48–0·80). Conclusions Patients who participated in the screening programme had lower mortality than those who had not undergone screening. However, these findings may result from a healthy screen bias and/or overdiagnosis associated with screening, and not from the screening itself.

Background It has not been conclusively established whether, or to what extent, the time to surgery affects mortality and the risk of complications after the surgical treatment of proximal femoral fractures. Methods Data on 106 187 hospitalizations over the period 2015-2017 involving insurees of the German AOK health insurance company aged 20 and above were drawn from pseudonymized billing data and stratified in three subgroups: osteosynthesis for pertrochanteric fracture (PTF-OS: N = 52 358), osteosynthesis for femoral neck fracture (FNF-OS: N = 7970), and endoprosthesis for femoral neck fracture (FNF-EP: N = 45 859). Multivariate regression models were used to analyze the relation between preoperative in-hospital stay (time to surgery, TTS: 0 days [reference category], 1, 2, 3, 4-7 days) and mortality and general complications within 90 days, with risk adjustment for fracture site, operative method, age, sex, accompanying illnesses, and antithrombotic medication in the preceding year. Results Mortality was significantly elevated only with PTF-OS, and only with a TTS of 2 days (odds ratio: 1.12 [95% confidence interval: (1.02; 1.23)]). General complications in relation to TTS were significantly elevated in the following situations: PTF-OS: 2 days: OR 1.24 [1.13; 1.37], 3 days: OR 1.33 [1.11; 1.60], 4-7 days: OR 1.47 [1.21; 1.78]; FNF-EP: 3 days: OR 1.21 [1.06; 1.37], 4-7 days: OR 1.42 [1.25; 1.62]; FNF-OS: 4-7 days: OR 1.86 [1.26; 2.73]. Conclusion A prolonged time to surgery is associated with an elevated general complication risk depending on the site of the fracture and the type of surgical procedure used.

In the legal domain, many legal documents such as court decisions and contracts are regularly anonymized. This process requires text sequences with high sensitivity to be identified and neutralized to secure sensitive information from third parties. Usually, this process is performed manually by trained employees. Therefore, anonymization is generally considered an expensive and inefficient process. This work proposes a machine learning approach for the automatic identification of sensitive text elements in German legal court decisions and provides an implementation. For this task, different deep neural network architectures based on generally pre-trained contextual embeddings as well as trained word embeddings are evaluated. Because of the lack of non-anonymized data sets, an approach to create pseudonymized data sets is proposed as well.

Background Few longitudinal studies investigate predictors of substance use incidence among immigrants. The current study describes substance use disorders in immigrants to Sweden, focusing on drinking culture in the country of origin and socioeconomic status (SES), and how these intersect with generational status to influence risk. Methods Using pseudonymized Swedish population registry data, we track onset of alcohol use disorder and drug use disorder in a longitudinal study of 815,778 first-generation immigrants and 674,757 second-generation immigrants from 64 countries over a 6-year period. Cox regression analysis estimated risks of alcohol and drug use disorders in second-generation immigrants compared to first-generation, and moderation analyses assessed interactions of generational status with country-of-origin per capita alcohol consumption and SES. Results Immigrants and second-generation immigrants originating from countries with high levels of alcohol consumption had higher risks for alcohol and drug use disorders. Immigrants with high SES had lower risks for alcohol and drug use disorders. The interaction between generational status and country-of-origin alcohol consumption was significant for drug use disorder (not for alcohol use disorder), with drug use disorder risk for second-generation immigrants being highest for those from countries with the lowest level of country-of-origin per capita alcohol consumption. The interaction between generational status and SES was significant for alcohol use disorder, with low-SES second-generation immigrants showing markedly higher risk than first-generation immigrants with comparable SES. Conclusions Among immigrants in Sweden, second-generation immigrants are at increased risk of developing alcohol and drug use disorders, particularly if they have lower SES. Policy and community attention to these high-risk subgroups in immigrant communities is warranted.

BACKGROUND The largest German study on place of death was performed for deaths in selected regions of Westphalia in the years 2001 and 2011. In the period thereafter, provision of palliative care was regionally expanded. This upgrade included the establishment of palliative medicine consultation services (PMCS), combining general and specialized palliative care on an outpatient basis. A follow-up place of death survey took place in 2017. The aim was to depict the trends in place of death between 2001 and 2017. A second goal was to determine how often outpatient PMCS were used by persons who died in 2017. METHODS Descriptive analysis of place of death as specified in all death certificates (2001, 2011, 2017) issued in the cities of Bochum and Munster and the districts of Borken and Coesfeld. Comparison of pseudonymized data on deceased patients (2017) treated by the PMCS of Munster and Coesfeld with the place of death database to ascertain the rate of PMCS care at the end of life. RESULTS A total of 38 954 death certificates were analyzed, and 5887 deaths were compared with PCMS data. The distribution of place of death was as follows: (2001, 2011, 2017; age standardized; %): own residence 27.8; 23.3; 21.3; hospital: 55.8; 51.8; 51.8; palliative care unit: 0.0; 1.0; 6.2; hospice: 1.9; 4.5; 4.8; nursing home: 13.1; 18.6; 20.4; other: 1.2; 1.2; 1.5. The rate of PMCS use was 28.8% (1694/5887). CONCLUSION Over the period 2001-2017, the proportion of people who died at home or in the hospital went down, while the number who died in a palliative care unit, hospice, or nursing home increased. In the city of Munster and the district of Coesfeld, one fourth of the people who died in 2017 received PMCS care at the end of life.

The present article portrays the use of “which is” as a currently popular mixed-code among Indonesians, especially teenagers and public figures, since the 2010s or popularly named as the language of South-Jakartans (Bahasa Anak Jaksel) by taking an Indonesian TV show as the data collection sites. The data were the comments of one of the judges of Indonesian Idol 2018, named ME. For investigation purpose, videos containing the “which is”phrase uttered by ME were sorted, transcribed, and analyzed. The analysis focused on how “which is”functions in the utterances. It was found that remarkable functions of “which is”include as substituting conjunctions and discourse markers. The substituting conjunctions include cause-effect and coordinating conjunctions, as for the discourse markers likely function to minimize face-threatening act.

Background/Purpose: To establish a high-quality vascular biomaterial bank to serve vascular research teams and act as a basis for translational medicine. The aim was to collect and store material so that investigation into the pathogenesis of vascular disease would be possible employing methods based on histopathology and/or molecular biology. Methods: The Vascular Biomaterialbank Heidelberg (VBBH) evolved as part of an established, partly accredited biobank complex at the University of Heidelberg (BioMaterialBank Heidelberg – BMBH). The BMBH provided infrastructure regarding legal and quality issues as well as safety, protocols for specimen collection, data management, and publication of results. Protocols were modified where necessary to accommodate specific needs of vascular tissue research. Correct identification of vascular biomaterial is controlled by certified vascular surgeons and pathologists at biobank entry and exit. Pseudonymized clinical data are attached to every specimen. Results: The VBBH provides standardized operating procedures (SOP) regulating the request, processing, and delivery of material to researchers, as well as project tracking. Tissue samples for a research project are requested by filling out an online application form. Within 3–5 working days, a scientific board, including a member of the VBBH and a member of the BMBH, decide upon acceptance or rejection of the research project. Criteria determining acceptance include whether enough samples are available for the particular investigation and whether planned methods are judged adequate to successfully complete the research project. Through tracking of all ongoing studies involving specimens from the VBBH, methods for tissue conservation are continually being optimized. The VBBH platform has supported numerous high-ranking publications involving diverse medical departments and reflects a gain in translational medicine. Conclusions: SOPs and controls by certified specialists ensure the high quality of specimens obtained through the VBBH. Research performed by vascular surgeons can be facilitated by using the VBBH.

Introduction Antibiotic consumption is highest in primary care, and antibiotic overuse furthers antimicrobial resistance. In our recently published pilot-RCT, we used monthly aggregated claims data to provide personalized antibiotic prescription feedback to general practitioners (GPs). The pilot-RCT has shown that personalized prescription feedback is a feasible and promising low-cost intervention to reduce antibiotic prescribing. Here, we describe the rationale and design of the follow-up RCT with 3426 GPs in Switzerland. We now have access to pseudonymized patient-level data from routinely collected health insurance data of the three largest health insurers in Switzerland. Methods and analysis 1713 GPs randomized to the intervention group received once evidence-based treatment guidelines at the beginning, including region-specific antibiotic resistance information from the community and personalized feedback of their antibiotic prescribing, followed by quarterly personalized prescription feedback for two years. The first and the last mailings were sent out in December 2017 and September 2019, respectively. The 1713 GPs randomized to the control group were not notified about the study and they received no guidelines and no prescription feedback. The personalized prescription feedbacks and the analyses of the primary and secondary outcomes are entirely based on pseudonymized patient-level data from routinely collected health insurance data. The primary outcome is prescribed antibiotics per 100 patient consultations during the second year of intervention. The secondary outcomes include antibiotic use during the entire two-year trial period, use of broad-spectrum antibiotics, hospitalization rates (all-cause and infection-related), and antibiotic use in different age groups. If the feedback intervention proves to be efficacious, the intervention could be continued systemwide. Ethics and dissemination The trial is publicly funded by the Swiss National Science Foundation (SNSF, grant number 407240_167066). The trial was approved by the ethics committee "Ethikkommission Nordwest-und Zentralschweiz" (EKNZ Project-ID 2017-00888). Results will be disseminated in peer-reviewed journals and international conferences., Highlights • The randomized trial design and blinding assure internal validity. • The use of routinely collected claims data maximizes the external validity. • The control group reflects the actual practice of antibiotic prescribing in primary care. • The primary analysis focuses on the longer-term effect of the feedback intervention. • The feedback intervention is inexpensive and could be continued systemwide.

The objective of this study is to provide an overview of the Regenstrief Teaching Electronic Medical Record (tEMR), how the tEMR could be used, and how it is currently being used in health professions education. The tEMR is a derivative of a real-world electronic health record (EHR), a large, pseudonymized patient database, and a population health tool designed to support curricular goals. The tEMR has been successfully adopted at 12 health professional, public health, and health information technology (HIT) schools, with over 11 800 unique student users and more than 74 000 logins, for case presentation, to develop diagnostic and therapeutic plans, and to practice documentation skills. With the exponential growth of health-related data and the impact of HIT on work-life balance, it is critical for students to get early EHR skills practice and understand how EHR’s work. The tEMR is a promising, scalable, flexible application to help health professional students learn about common HIT tools and issues.

Real-world data are crucial to continuously improve the management of patients with rheumatic and musculoskeletal diseases (RMDs). The German RheumaDatenRhePort (RHADAR) registry encompasses a network of rheumatologists and researchers in Germany providing pseudonymized real-world patient data and allowing timely and continuous improvement in the care of RMD patients. The RHADAR modules allow automated anamnesis and adaptive coordination of appointments regarding individual urgency levels. Further modules focus on the collection and integration of electronic patient-reported outcomes in between consultations. The digital RHADAR modules ultimately allow a patient-centered adaptive approach to integrated medical care starting as early as possible in the disease course. Such a closed-loop system consisting of various modules along the whole patient pathway enables comprehensive and timely patient management in an unprecedented manner.

The unique properties of blockchain enable central requirements of distributed secure logging: Immutability, integrity, and availability. Especially when providing transparency about data usages, a blockchain-based secure log can be beneficial, as no trusted third party is required. Yet, with data governed by privacy legislation such as the GDPR or CCPA, the core advantage of immutability becomes a liability. After a rightful request, an individual's personal data need to be rectified or deleted, which is impossible in an immutable blockchain. To solve this issue, we exploit a legal property of pseudonymized data: They are only regarded personal data if they can be associated with an individual's identity. We make use of this fact by presenting P3, a pseudonym provisioning system for secure usage logs including a protocol for recording new usages. For each new block, a one-time transaction pseudonym is generated. The pseudonym generation algorithm guarantees unlinkability and enables proof of ownership. These properties enable GDPR-compliant use of blockchain, as data subjects can exercise their legal rights with regards to their personal data. The new-usage protocol ensures non-repudiation, and therefore accountability and liability. Most importantly, our approach does not require a trusted third party and is independent of the utilized blockchain software., Comment: Peer-reviewed version accepted for publication in the proceedings of the 2021 International Conference on Evaluation and Assessment in Software Engineering (EASE'21)

Background The impact of the COVID-19 outbreak and lockdown in liver transplant (LT) patients remains unknown. The aim of this cross-sectional study was to assess the consequences of the COVID-19 pandemic on the physical and mental health of LT patients during the lockdown period. Methods Between August and October 2020 a Web-based questionnaire was emailed to 238 LT patients undergoing regular follow-up at our unit. This pseudonymized survey explored demographic and lifestyle variables (i.e. eating and physical habits), disruptions in routine medical care, and different dimensions of mental health, COVID-19-related mood and coping (worries/anxiety, depression, insomnia, fear of Covid, resilience, etc.), and health perception using different validated instruments. Results 48.7% (116 of 238) LT recipients accepted to participate, 104 of whom gave their consent to publish the data. The median age was 63 years. Up to 39.4% presented worrying scores indicating moderate/severe generalized anxiety disorder (GAD), whereas 25.5% exhibited moderate/severe insomnia and only 10.5% moderate/severe depression. Forty patients (38.5%) gained weight, 24% experienced a worsening in their eating habits and 63.4% referred to practice less or much less exercise during the lockdown. Only 25% perceived a worsening in the control of their chronic comorbidities. Missed medical appointments (0.9%) or worsening adherence to therapy (1.9%) were exceptional. Conclusions COVID-19 lockdown has negatively impacted the mental and physical health of LT patients. Long-term consequences remain unclear.

Background eHealth and mobile health (mHealth) are an evolving trend in the medical field. The acceptance of digital tools is high, and the need is growing. Objective Young adults (18-40 years) confronted with a cancer diagnosis present unique needs and require special care. They often have a strong affinity and are familiar with modern technology. On that account, we implemented a web-based symptom and quality of life (QoL) assessment to address patients’ attitudes and willingness to use mHealth tools. The study also aims to evaluate sociodemographic parameters that could influence patients’ opinions. Methods A total of 380 young patients aged 18-40 treated with radiotherapy between 2002 and 2017 were included in the trial. We assessed QoL via the European Organization for Research and Treatment of Cancer-Core 30 (EORTC C30) questionnaire and added general questions about mHealth technology. The added questions inquired patients’ opinions regarding general aspects, including technical advances in medicine, mobile and app assistance during cancer treatment, data transfer, and app-specific features. The survey was conducted for 12 months. Participation was voluntary and pseudonymized; prior written consent was obtained. Results We achieved a participation rate of 57.6% (219/380) and a completion rate of 50.2% (110/219). The median age was 33 years (range 18-40). Of all participants, 89.1% (98/110) considered new technologies in medicine as positive; 10.9% (12/110) answered with neutral. Nearly all patients (96.4%, 106/110) stated that they would send further data via a web-based platform. Of all, 96.4% (106/110) considered the provided pseudonymization of their data as safe. We further asked the patients if they would use a mobile app for symptom and QoL assessment similar to the present web-based system: 74.5% (82/110) answered with yes and 25.5% (28/110) said they would not use a mobile app in the future. We tested the willingness to use an app on several sociodemographic parameters, such as age, gender, education, health insurance status, and cancer-related parameters: tumor stage, time since radiation treatment, and treatment intention. None of these parameters correlated with app use in this group of young adults. Patients who were generally positive regarding using an app rated several possible functions of a future app. The 3 most requested features were appointment reminders (89.0%, 73/82), contact overview of all involved clinics and physicians (87%, 71/82), and making an appointment via app (78%, 64/82). Conclusions eHealth and mHealth tools should be available as an integrated part of a comprehensive cancer care approach. It provides automated, thorough documentation of health parameters during therapy and follow-up for doctors, medical staff, and tumor patients to optimize treatment. With this study, we could show that young adults are the ideal patient population to use eHealth/mHealth tools. Such tools offer further digital support and improve the patients’ need for constant QoL during cancer care.

The three-armed cluster-randomized trial ARena (sustainable reduction of antibiotic-induced antimicrobial resistance) aimed to foster appropriate antibiotic use and reduce overprescribing in German ambulatory care to counter antibiotic resistance. Multi-faceted interventions targeted primary care physicians, teams and patients. This study examined the effectiveness of the implementation program. ARena was conducted in 14 primary care networks with 196 practices. All arms received data-based feedback on antibiotics prescribing and quality circles. Arms II and III received different add-on components each. Primary outcome examined is the prescribing rate for systemic antibiotics for cases with non-complicated acute infections (upper respiratory tract, bronchitis, sinusitis, tonsillitis, otitis media). Secondary outcomes refer to the prescribing of quinolones and guideline-recommended antibiotics. Based on pseudonymized quarterly claims data, mixed logistic regression models examined pre-post intervention antibiotic prescribing rate changes and compared to matched standard care. A significant rate reduction (arm I 11.7%, arm II 9.9%, arm III 12.7%) and significantly lower prescribing rates were observed for all arms (20.1%, 18.9% and 23.6%) compared to matched standard care (29.4%). Fluoroquinolone prescribing was reduced in all intervention arms and rates for recommended substances generally increased. No significant post-interventional difference between intervention arms was detected. Findings indicate implementation program impact compared to standard care.

Personal medical information is an essential resource for research; however, there are laws that regulate its use, and it typically has to be pseudonymized or anonymized. When data are anonymized, the quantity and quality of extractable information decrease significantly. From the perspective of a clinical researcher, a method of achieving pseudonymized data without degrading data quality while also preventing data loss is proposed herein. As the level of pseudonymization varies according to the research purpose, the pseudonymization method applied should be carefully chosen. Therefore, the active participation of clinicians is crucial to transform the data according to the research purpose. This can contribute to data security by simply transforming the data through secondary data processing. Case studies demonstrated that, compared with the initial baseline data, there was a clinically significant difference in the number of datapoints added with the participation of a clinician (from 267,979 to 280,127 points, P < 0.001). Thus, depending on the degree of clinician participation, data anonymization may not affect data quality and quantity, and proper data quality management along with data security are emphasized. Although the pseudonymization level and clinical use of data have a trade-off relationship, it is possible to create pseudonymized data while maintaining the data quality required for a given research purpose. Therefore, rather than relying solely on security guidelines, the active participation of clinicians is important., Graphical Abstract

To assess accurately the risk of being compromised, anonymized data requires a balance between utility and security. This paper studies the risk of reidentification for long-term transaction records aggregated by pseudonym (pid). Given a set of transaction records with pseudonyms, an adversary attempts to identify individuals by maximizing the similarity between sets of goods that have been purchased using the pseudonyms. Assuming a uniform probability for the choice of goods and applying Zipf’s law to the behavior of the number of records per individual, we investigate the likelihood of an individual being correctly reidentified. Our model reveals that the risk of reidentification increases as the number of records associated with the pseudonym increases. A similar effect in terms of risk and the number of pseudonyms was found in a competition for data anonymization (PWS Cup 2017), where the Online Retail dataset comprising 40,000 records for 500 individuals was securely anonymized by each team and then reidentified each other. The competition results suggested that the reidentification rate increases the longer a pseudonym remains unchanged.

Objectives Maternal obesity during pregnancy is associated with adverse intrauterine events and fetal outcomes and may increase the risk of obesity and metabolic disease development in offspring. Higher parity, regardless of socioeconomic status, is associated with increased maternal body mass index (BMI). In this study, we examined the relationship between parity, maternal obesity, and fetal outcomes in a large sample of mother-neonate pairs from Lower Saxony, Germany. Methods This retrospective cohort study examined pseudonymized data of a non-selected singleton cohort from Lower Saxony’s statewide quality assurance initiative. 448,963 cases were included. Newborn outcomes were assessed in relation to maternal BMI and parity. Results Maternal obesity was associated with an increased risk of placental insufficiency, chorioamnionitis, and fetal distress while giving birth. This effect was present across all parity groups. Fetal presentation did not differ between BMI groups, except for the increased risk of high longitudinal position and shoulder dystocia in obese women. Maternal obesity was also associated with an increased risk of premature birth, low arterial cord blood pH and low 5-min APGAR scores. Conclusions Maternal obesity increases the risk of adverse neonatal outcomes. There is a positive correlation between parity and increased maternal BMI. Weight-dependent fetal risk factors increase with parity, while parity-dependent outcomes occur less frequently in multipara. Prevention and intervention programs for women planning to become pregnant can be promising measures to reduce pregnancy and birth complications.

Highlights • Children’s understanding of epilepsy reflects their lived experiences. • Parents are key information gatekeepers and shape children’s understanding. • Children face challenges in being meaningfully involved in healthcare decisions., Purpose To use a qualitative research approach to determine children’s understandings of epilepsy and their epilepsy treatment. Methods Children aged 7–16 years with physician-confirmed active epilepsy (i.e., having had an epileptic seizure in the past year and or currently taking antiepileptic drugs (AEDs), and not known to have an intellectual disability, were invited to participate. Children had semi-structured interviews separately on two occasions. Between the first and second interviews, an observation of a routine epilepsy clinic appointment of individual children was conducted, and was then discussed during the second interview. Participatory research tools were used in both child interviews to facilitate discussions. Interviews were audio recorded and transcribed, pseudonymized and entered into NVivo (version 12, QSR International). Data were analyzed using a thematic approach. Results Twenty-three children of mean age 10.1 years (range 8–14), mean duration of epilepsy of 4.6 years (range 2–10) were enrolled. Twelve were 12 female; 7 had focal, 14 had generalized, and 2 had combined epilepsy; 20 were on monotherapy; and 16 had tried previous AEDs. All had an initial (first) interview; 20 were observed during a clinic appointment and had a second interview. Five broad themes emerged: understanding of epilepsy; understanding of seizures; understanding of medication; understanding of children’s role in clinical appointments; influences on children’s understanding. Children spoke about what epilepsy meant by describing the physical sensations of having a seizure or through the act of taking medication. Children described the role they had, or felt they should have, but reported challenges in being meaningfully involved in clinical appointments. While healthcare professionals were initial information nodes, epilepsy information from parents appeared to be more significant for children. Conclusions The perspectives of children with epilepsy are valuable for clinicians to understand; assumptions should not be made that children’s views can be accessed via parents. Clinicians need to be constantly aware of children’s views and ways of understanding and communicating about their epilepsy. To support this, the research – drawing on children’s words, meanings, and stories – was used to inform an easily accessible, gender-neutral, animation about epilepsy that provides information about the condition, seizures, and medication (https://youtu.be/MO7xXL2ZXP8).

BackgroundRecord linkage is increasingly used in health research worldwide. Combining the patient information available in healthcare, administrative and clinical databases broadens the research perspectives, particularly for chronic diseases. Recent guidelines highlight the need for transparency on the used record linkage processes and the extracted data to be used by researchers.MethodsTherefore, the aim of this study was to describe the deterministic iterative approach used to link the French Epidemiology and Information Network (REIN), a French national End-Stage Renal Disease registry, with the Système National des Données de Santé (SNDS), a French nationwide medico-administrative healthcare database.ResultsAmong the 22,073 patients included in the REIN registry who started renal replacement therapy between 2014 and 2015 in France, 19,223 (87.1%) were matched with patients in the SNDS database. Comparison of matched and unmatched patients confirmed the absence of any major selection bias. Then, the record linkage was evaluated using the comorbidity status (diabetes).ConclusionsThis fast and efficient method of record linkage with pseudonymized data and without unique and direct identifier might inspire other research teams. It also opens the path for new research on chronic kidney disease.

Identifying people from anonymous location histories is important for two purposes. i.e. to clarify privacy risks in using the location histories and to find evidence of who went where and when. Although linking with social network accounts is an excellent approach for such identification, previous methods need information about social relationships and have a limitation on the number of target data sets. Moreover, they make limited use of time information. We present models that overcome these problems by estimating the sameness and difference of people by using combinations of time and distance. Our proposed method uses these models along with multi-resolution models for both sides of linking, i.e. location histories and social network accounts. Evaluation using real data demonstrated the effectiveness of our method even when linking only one pseudonymized and obfuscated location history to 1 of 10,000 social network accounts without any information about social relationships.

In response to the coronavirus disease 2019 (COVID-19) pandemic, governments have encouraged and ordered citizens to practice social distancing, particularly by working and studying at home. Intuitively, only a subset of people have the ability to practice remote work. However, there has been little research on the disparity of mobility adaptation across different income groups in US cities during the pandemic. The authors worked to fill this gap by quantifying the impacts of the pandemic on human mobility by income in Greater Houston, Texas. In this paper, we determined human mobility using pseudonymized, spatially disaggregated cell phone location data. A longitudinal study across estimated income groups was conducted by measuring the total travel distance, radius of gyration, number of visited locations, and per-trip distance in April 2020 compared to the data in a baseline. An apparent disparity in mobility was found across estimated income groups. In particular, there was a strong negative correlation ($\rho$ = -0.90) between a traveler's estimated income and travel distance in April. Disparities in mobility adaptability were further shown since those in higher income brackets experienced larger percentage drops in the radius of gyration and the number of distinct visited locations than did those in lower income brackets. The findings of this study suggest a need to understand the reasons behind the mobility inflexibility among low-income populations during the pandemic. The study illuminates an equity issue which may be of interest to policy makers and researchers alike in the wake of an epidemic., Comment: 13 pages, 7 figures

Background gdT-cells are attractive targets for cancer immunotherapy given their strong cytolytic and pro-inflammatory cytokine secretion activities, and the association between tumor infiltration and positive prognosis.1 2 ImCheck Therapeutics is developing ICT01, an anti-human butyrophilin-3A (BTN3A/CD277) mAb specifically activating g9d2 T-cells in a phosphoantigen (pAg)-independent manner. ICT01 is currently in a Phase 1/2a study in solid and hematologic tumors (NCT04243499).IL-2 has been shown to expand g9d2 T-cells in vitro and in non-human primates in presence of pAgs.3 4 5 We wanted to characterize the proliferative effects of combining ICT01 with IL-2 on γ9δ2 T-cells as an approach to potentiate g9d2 T-cell mediated cancer immunotherapy. Methods g9d2 T-cell activation and expansion was assessed in vitro in human PBMCs treated with ICT01±IL-2, and in vivo, in the blood of immunocompromised NCG mice engrafted with 20 × 106 human PBMCs and treated with ICT01 (single IV dose, 5 mg/kg on Day 1) ±IL-2 (0.3MIU/kg IP on Day 1–4). A dose-ranging ICT01 (single IV dose, 1 or 5 mg/kg on Day 1)+IL-2 combination (1 MIU SC QD on Days 1–5) study was conducted in cynomolgus monkeys. Results In PBMCs cultures in vitro, ICT01 selectively activated g9d2 T-cells and IL-2 significantly enhanced ICT01-mediated g9d2 T-cell proliferation, this compartment reaching >50% of T-cells after 8 days of treatment versus ~10% with ICT01 alone. This was confirmed in vivo in mice models. Flow cytometry analysis of mice blood revealed a 5.5-fold increase in human g9d2 T-cell number in the combination groups compared to ICT01 or IL-2 alone treated animals, with g9d2 T-cell frequency reaching ~35% of the CD3+ T-cell compartment. In Cynomolgus, a specific expansion and activation of peripheral g9d2 T-cells from ~1–2% at baseline to up to 30% of T cells 7 days post ICT01 administration was observed. No ICT01 effect was observed on other immune cells. Histopathological examinations revealed a trend towards higher numbers of g9d2 T-cells in several organs in ICT01+IL-2 treated monkeys. There was no evidence for a systemic cytokine release syndrome at any time point. Adverse effects with variable severity were observed, most of them being reversible and commonly associated with IL-2 alone, and not reported in the IND-enabling GLP toxicity study with ICT01 monotherapy at doses up to 100 mg/kg. Conclusions These results demonstrate the ability of ICT01+IL-2 combination to trigger profound γ9δ2 T-cell activation and expansion, suggesting that the clinical combination of ICT01 with a lymphoproliferative cytokine (e.g., IL-2) may be a novel therapeutic approach for cancer patients. Ethics Approval Pseudonymized samples isolated from healthy volunteers: whole blood by ImCheck Therapeutics under the agreement n° 7173 between ImCheck Therapeutic SAS and EFS PACA (Etablissement Francais du Sang Provence-Alpes-cote d’Azur) References Gentles AJ, Newman AM, Liu CL, et al. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nature Medicine 2015;21(8):938–945. Tosolini M, Pont F, Poupot M, et al. Assessment of tumor-infiltrating TCRVγ9Vδ2 γδ lymphocyte abundance by deconvolution of human cancers microarrays. OncoImmunology 2017;6(3):e1284723. Nada MH, Wang H, Workalemahu G, Tanaka Y, Morita CT. Enhancing adoptive cancer immunotherapy with Vγ2Vδ2 T cells through pulse zoledronate stimulation. Journal for ImmunoTherapy of Cancer 2017;5(1):9. Sicard H, Ingoure S, Luciani B, et al. In Vivo Immunomanipulation of Vγ9Vδ2 T cells with a synthetic phosphoantigen in a preclinical nonhuman primate model. The Journal of Immunology 2005;175(8):5471–5480. Ali Z, Shao L, Halliday L, et al. Prolonged (E)-4-Hydroxy-3-Methyl-But-2-Enyl pyrophosphate-driven antimicrobial and cytotoxic responses of pulmonary and systemic Vγ2Vδ2 T cells in macaques. The Journal of Immunology 2007;179(12):8287–8296.

Background gdT-cells are innate-like lymphocytes described as potent killer of cancer cells whose infiltration into tumors is associated with a positive prognosis.1 2 This supports gd T-cells use in cancer immunotherapy. BTN3A, which belongs to the B7-subfamily of Ig proteins, is required for the recognition of malignant or infected cells by human g9d2 T-cells by sensing intracellular accumulation of phosphoantigens.3 ImCheck Therapeutics is developing ICT01, a humanized anti-BTN3A (IgG1, Fc-silenced), g9d2 T-cell-activating antibody for the treatment of patients with solid or hematologic tumors. Methods A complete IND-enabling program was conducted to characterize the preclinical activity and safety of ICT01. ICT01 effects on human and cynomolgus PBMCs were characterized in vitro using flow cytometry. ICT01-mediated killing activity of g9d2 T-cells was assessed using in vitro co-cultures with tumor and non-tumor cells. Immunocompromised mice bearing human tumors and adoptively transferred with human g9d2 T cells were used to assess ICT01 anti-tumor activity in vivo. The PK, PD and safety of intravenous ICT01 (0.1 to 100 mg/kg single- and repeated-dose) were evaluated in Cynomolgus monkeys. Results ICT01 selectively binds to all three BTN3A isoforms with high affinity ( Conclusions The combined in vitro and in vivo pharmacology data provide evidence that ICT01 is an attractive and novel therapeutic approach for enhancing the innate anti-tumor potential of g9d2 T-cells by activating BTN3A. Importantly, ICT01 did not affect healthy BTN3A-expressing cells, and NHP studies confirmed ICT01 safety with a wide therapeutic index. Therefore, ICT01 is being tested in the ongoing EVICTION trial (NCT04243499). Ethics Approval Pseudonymized samples isolated from healthy volunteers’ whole blood by ImCheck Therapeutics under the agreement n° 7173 between ImCheck Therapeutic SAS and EFS PACA (Etablissement Francais du Sang Provence-Alpes-cote d’Azur) References Gentles AJ, Newman AM, Liu CL, et al. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nature Medicine 2015;21(8):938–945. Tosolini M, Pont F, Poupot M, et al. Assessment of tumor-infiltrating TCRVγ9Vδ2 γδ lymphocyte abundance by deconvolution of human cancers microarrays. OncoImmunology. 2017;6(3):e1284723. Harly C, Guillaume Y, Nedellec S, et al. Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human γδ T-cell subset. Blood 2012;120(11):2269–2279.

Background:Early diagnosis and reliable differentiation between rheumatic diseases (RMDs) are crucial to start an adequate therapy and prevent irreversible damage. Since finger joints are commonly affected in rheumatoid arthritis (RA) and psoriatic arthritis (PsA), imaging of the peripheral skeleton is an essential step of diagnosis at a rheumatologist. High resolution peripheral quantitative computed tomography (HR-pQCT) allows an even more detailed and three-dimensional (3D) illustration of the peripheral bone than conventional radiographs. Segmented scans contain further information, such as the density, microstructure, and shape of the bones, which can be further analyzed by neural networks.Objectives:We hypothesize that, based on the shape of the second metacarpophalangeal (MCP) joint from HR-pQCT images, a neural network can be trained to differentiate between RA, PsA, and healthy controls and to reveal regions in the bone shape characteristic for the diseases.Methods:HR-pQCT images of MCP joints from patients with classified CCP positive RA, classified PsA, and healthy controls with low motion artifacts and appropriate scan region were selected as reported previously [3]. Scans were performed as part of the clinical routine and patients gave their informed consent to use pseudonymized data (Ethics approval 334_16B). Based on the assumption that pathognomonic changes develop over time, only images were used, where the period between classification and imaging exceeded one year.Based on previous work [4], a pixel-wise mask of the second metacarpal bone was generated using a neural network based on the HR-pQCT scans of patients. Supervised auto-encoder [1] networks were used to predict the correct class given the bone mask only. For the neural network experiment, the patient scans were split on a patient-level into training (70%), validation (20%), and testing (10%). Guided backpropagation [2] was used as a method to investigate the regions influencing the class prediction most.Results:In total, images of 331 patients were included in the experiments. The evaluation of the model on the 33 test cases yielded a high accuracy for the healthy control with 94%, RA patients with 84%, and PsA patients with 89%. An area under the receiver operator curve of 91% could be achieved. The regions of the bone mask influencing the network´s decision most are highlighted exemplary in Figure 1.Figure 1.Visualization of the HR-pQCT slices with gradient maps. Higher values (red) represent regions that had a stronger contribution to the classification result. The HR-pQCT images are displayed for reference only. (a) Healthy patient, (b) RA diagnosed patient, and (c) PsA diagnosed patient. The first row shows the single slices with the highest values corresponding to the 3D bone masks in the second row.Conclusion:For the first time, a neural network-based approach successfully provides a differential diagnosis of RA and PsA based only on the shape of the second MCP in HR-pQCT images. The evaluation of the test set suggests that high curvatures of the bone surface in the joint region significantly influence the prediction of the network, suggesting an in-depth investigation of these regions for patients affected by RA and PsA. Based on these promising findings, we aim to extend the approach to seronegative RA as well as early RA and PsA.References:[1]Le, L. et al. (2018). Supervised autoencoders: Improving generalization performance with unsupervised regularizers. In Advances in Neural Information Processing Systems.[2]Springenberg, J. T. et al. (2015). Striving for simplicity: The all convolutional net. 3rd International Conference on Learning Representations, ICLR 2015 - Workshop Track Proceedings.[3]Simon, D. et al. (2017). Age- and Sex-Dependent Changes of Intra-articular Cortical and Trabecular Bone Structure and the Effects of Rheumatoid Arthritis. Journal of Bone and Mineral Research, 32(4), 722–730.[4]Folle, L. et al. (2021). Fully Automatic Bone Mineral Density Measurements using Deep Learning. Manuscript submitted for publication.Acknowledgements:This work was supported by the emerging field initiative (project 4 Med 05 “MIRACLE”) of the University Erlangen-Nürnberg and MASCARA - Molecular Assessment of Signatures Characterizing the Remission of Arthritis grant 01EC1903A.Disclosure of Interests:Lukas Folle: None declared, Chang Liu: None declared, David Simon Speakers bureau: Lilly, Novartis, Consultant of: Lilly, Novartis, Gilead, BMS, Abbvie, Grant/research support from: Lilly, Novartis, Timo Meinderink: None declared, Anna-Maria Liphardt Consultant of: Mylan/Meda Pharma, Grant/research support from: Novartis, Gerhard Krönke Speakers bureau: Lilly, Novartis, Consultant of: Lilly, Novartis, Gilead, BMS, Abbvie, Grant/research support from: Lilly, Novartis, Georg Schett Speakers bureau: Lilly, Novartis, Consultant of: Lilly, Novartis, Gilead, BMS, Abbvie, Grant/research support from: Lilly, Novartis, Andreas Maier: None declared, Arnd Kleyer Speakers bureau: Lilly, Novartis, Consultant of: Lilly, Novartis, Gilead, BMS, Abbvie, Grant/research support from: Novartis, Lilly

Background Evaluating the completeness of tuberculosis (TB) notification data is important for monitoring of TB surveillance systems. We conducted an inventory study to calculate TB underreporting in Germany in 2013–2017. Methods Acquisition of two pseudonymized case-based data sources (national TB notification data and antibiotic resistance surveillance data) was followed by two-source Capture-recapture (CRC) analysis, as case-based data from a third source was unavailable. Aggregated data on consumption of a key anti-TB drug (pyrazinamide [PZA]) was compared to an estimated need for PZA based on TB notification data to obtain an independent underreporting estimation. Additionally, notified TB incidence was compared to TB rate in an aggregated health insurance fund dataset. Results CRC and PZA-based approaches indicated that between 93 and 97% (CRC) and between 91 and 95% (PZA) of estimated cases were captured in the national TB notification data in the years 2013–2017. Insurance fund dataset did not indicate TB underreporting on the national level in 2017. Conclusions Our results suggest that more than 90% of estimated TB cases are captured within the German TB surveillance system, and accordingly the TB notification rate is likely a good proxy of the diagnosed TB incidence rate. An increase in underreporting and discrepancies however should be further investigated.

Background The aim of this study is to investigate the potential impact of prostate magnetic resonance imaging (MRI) -related interreader variability on a population-based randomized prostate cancer screening trial (ProScreen). Methods From January 2014 to January 2018, 100 men aged 50–63 years with clinical suspicion of prostate cancer (PCa) in Helsinki University Hospital underwent MRI. Nine radiologists individually reviewed the pseudonymized MRI scans of all 100 men in two ProScreen trial centers. All 100 men were biopsied according to a histological composite variable comprising radical prostatectomy histology (N = 38) or biopsy result within 1 year from the imaging (N = 62). Fleiss’ kappa (κ) was used to estimate the combined agreement between all individual radiologists. Sample data were subsequently extrapolated to 1000-men subgroups of the ProScreen cohort. Results Altogether 89% men of the 100-men sample were diagnosed with PCa within a median of 2.4 years of follow-up. Clinically significant PCa (csPCa) was identified in 76% men. For all PCa, mean sensitivity was 79% (SD ±10%, range 62–96%), and mean specificity 60% (SD ±22%, range 27–82%). For csPCa (Gleason Grade 2–5) MRI was equally sensitive (mean 82%, SD ±9%, range 67–97%) but less specific (mean 47%, SD ±20%, range 21–75%). Interreader agreement for any lesion was fair (κ 0.40) and for PI-RADS 4–5 lesions it was moderate (κ 0.60). Upon extrapolating these data, the average sensitivity and specificity to a screening positive subgroup of 1000 men from ProScreen with a 30% prevalence of csPCa, 639 would be biopsied. Of these, 244 men would be true positive, and 395 false positive. Moreover, 361 men would not be referred to biopsy and among these, 56 csPCas would be missed. The variation among the radiologists was broad as the least sensitive radiologist would have twice as many men biopsied and almost three times more men would undergo unnecessary biopsies. Although the most sensitive radiologist would miss only 2.6% of csPCa (false negatives), the least sensitive radiologist would miss every third. Conclusions Interreader agreement was fair to moderate. The role of MRI in the ongoing ProScreen trial is crucial and has a substantial impact on the screening process.

Background Infectious diseases, such as HCV infection, HBV infection and syphilis, put a huge burden on public health. Accurate and fast testing is required for clinical usage. Objectives This study aimed to evaluate the clinical performance of Elecsys® Anti−HCV II, Elecsys® HBsAg II and Elecsys® Syphilis using samples from routine diagnosis in China. Methods Specificity was tested in approximately 3000 unselected pseudonymized samples from routine clinical patients for each assay. Sensitivity of HCV and HBsAg assays was tested in 2 seroconversion panels, respectively. Results The 3 investigational assays on cobas e 801 were showed to have excellent sensitivity and specificity which is comparable to existing assays. Conclusion They are suitable for routine clinical diagnostic use, including pre-operative assessment in China.

Purpose: MR-guided Radiation Therapy (MRgRT) allows for high-precision radiotherapy under real-time MR visualization. This enables margin reduction and subsequent dose escalation which may lead to higher tumor control and less toxicity. The Unity MR-linac (Elekta AB, Stockholm, Sweden) integrates a linear accelerator with a 1.5T diagnostic quality MRI and an online adaptive workflow. A prospective international registry was established to facilitate the evidence-based implementation of the Unity MR-linac into clinical practice, to systemically evaluate long-term outcomes, and to aid further technical development of MR-linac-based MRgRT. Methods and Results: In February 2019, the Multi-OutcoMe EvaluatioN of radiation Therapy Using the MR-linac study (MOMENTUM) started within the MR-linac Consortium. The MOMENTUM study is an international academic-industrial partnership between several hospitals and industry partner Elekta. All patients treated on the MR-linac are eligible for inclusion in MOMENTUM. For participants, we collect clinical patient data (e.g., patient, tumor, and treatment characteristics) and technical patient data which is defined as information generated on the MR-linac during treatment. The data are captured, pseudonymized, and stored in an international registry at set time intervals up to two years after treatment. Patients can choose to provide patient-reported outcomes and consent to additional MRI scans acquired on the MR-linac. This registry will serve as a data platform that supports multicenter research investigating the MR-linac. Rules and regulations on data sharing, data access, and intellectual property rights are summarized in an academic-industrial collaboration agreement. Data access rules ensure secure data handling and research integrity for investigators and institutions. Separate data access rules exist for academic and industry partners. This study is registered at ClinicalTrials.gov with ID: NCT04075305 (https://clinicaltrials.gov/ct2/show/NCT04075305). Conclusion: The multi-institutional MOMENTUM study has been set up to collect clinical and technical patient data to advance technical development, and facilitate evidenced-based implementation of MR-linac technology with the ultimate purpose to improve tumor control, survival, and quality of life of patients with cancer.

Background Defining incident cases has always been a challenging issue for researchers working with routine data. Lookback periods should enable researchers to identify and exclude recurrent cases and increase the accuracy of the incidence estimation. There are different recommendations for lookback periods depending on a disease entity of up to 10 years. Well-known drawbacks of the application of lookback periods are shorter remaining observation period in the dataset or smaller number of cases. The problem of selectivity of the remaining population after introducing lookback periods has not been considered in the literature until now. Methods The analyses were performed with pseudonymized claims data of a German statutory health insurance fund with annual case numbers of about 2,1 million insured persons. Proportions of study population excluded due to the application of lookback periods are shown according to age, occupational qualification and income. Myocardial infarction and stroke were used to demonstrate changes in incidence rates after applying lookback periods of up to 5 years. Results Younger individuals show substantial dropouts after the application of lookback periods. Furthermore, there are selectivities regarding occupational qualification and income, which cannot be handled by age standardization. Due to selective dropouts of younger individuals, crude incidence rates of myocardial infarction and stroke increase after applying lookback periods. Depending on the income group, age-standardized incidence rates changed differentially, leading to a decrease and possible underestimation of the social gradient after applying lookback periods. Conclusions Selectivity analyses regarding age and sociodemographic structure should be performed for the study population after applying lookback periods since the selectivity can affect the outcome especially in health care research. The selectivity effects might occur not only in claims data of one health insurance fund, but also in other longitudinal data with left- or right-censoring not covering the whole population. The effects may also apply to health care systems with a mix of public and private health insurance. A trade-off has to be considered between selectivity effects and eliminating recurrent events for more accuracy in the definition of incidence.

UK Biobank is an international health resource enabling research into the genetic and lifestyle determinants of common diseases of middle and older age. It comprises 500,000 participants. Public Health England’s Second Generation Surveillance System is a centralized microbiology database covering English clinical diagnostics laboratories that provides national surveillance of legally notifiable infections, bacterial isolations and antimicrobial resistance. We previously developed secure, anonymized, individual-level linkage of these systems. In this study, we implemented rapid dynamic linkage, which allows us to provide a regular feed of new COVID-19 (SARS-CoV-2) test results to UK Biobank to facilitate rapid and urgent research into the epidemiological and human genetic risk factors for severe infection in the cohort. Here, we have characterized the first 678 cases of COVID-19 in UKB participants, of whom 552 met our working definition of severe COVID-19 as inpatients hospitalized on or after 16 March 2020. We found that the incidence of severe COVID-19 among UKB cases was 27.1% lower than the general population in England, although this difference varied significantly by age and sex. The total number of UKB cases comprised could be estimated as 0.9% of the publicly announced number of cases in England. We considered how increasing case numbers will affect the power of genome-wide association studies. This new dynamic linkage system has further potential to facilitate the investigation of other infections and the prospective collection of microbiological cultures to create a microbiological biobank (‘bugbank’) for studying the interaction of environment, human and microbial genetics on infection in the UK Biobank cohort.

Introduction “Transgender” and “gender diverse” are umbrella terms encompassing those whose gender identities or expressions differ from those typically associated with the sex they were assigned at birth. There is scant global information on cancer incidence, outcome, and mortality for this cohort. This group may present with advanced cancer, have mistrust in health care services and report anxiety and depression at higher frequencies, a finding often seen in marginalized groups because of minority stress. Materials and Methods Medical oncologists were contacted by secure email to identify patients who self-identify as transgender and gender diverse in three Irish hospitals. Five patients were identified. A retrospective chart review was conducted and a pseudonymized patient survey was distributed. Results All patients included in our chart review (n = 5) were diagnosed with advanced disease on initial diagnosis. Two patients identified as men, two as women, and one as a transwoman. Two of five patients' health record charts reflected a name or gender change. Three patients had gender transitioning treatment postponed. Assessing comorbidities, it was seen that four patients required psychiatry input. Predominant issues noted in our patient survey by the two respondents (n = 2) were “mis-gendering,” lack of a gender-neutral hospital environment, lack of inclusion in cancer groups, and barriers in changing name and/or sex on hospital records. Conclusion Components of care requiring revision include patient accessible pathways to change names and gender on health records, earlier access to psychological support and targeted screening and support groups. Resources for hospital staff to improve awareness of correct terminology and to provide gender neutral facilities are worthwhile. Implications for Practice The implications for practice on an international level include patient-friendly pathways for changing hospital name and gender so that patients may feel comfortable using wristbands. The need for international screening guidelines for transgender patients and national transgender cancer support groups is highlighted. On a day-to-day level for providers, the correct use of pronouns makes a big difference to patients. Asking about preferred pronoun on first visit and noting on patient's file is worthwhile. It is important for providers to know that increased psychological support should be offered early on first clinic visit and engaged with as necessary when patient has a history of anxiety or depression. Providers should discuss openly that some gender transitioning treatment will be postponed because of cancer care and refer to both the physical and psychological sequelae of this. Asking transgender patients which room or bathroom they would prefer when rooms are gendered is essential.